DESCRIPTION (Applicant's Description) Colorectal cancer (CRC) screening reduces mortality, but it remains unclear whether the combination of a fecal occult blood test (FOBT) and sigmoidoscopy offers any advantage over either method used alone. Kaiser Permanente has begun a population CRC screening program based on the use of sigmoidoscopy every 10 years. FOBT has not been included due to the low sensitivity of unrehydrated Hemoccult and the low specificity of the rehydrated Hemoccult. A combination FOBT consisting of a high sensitivity guaiac-based test (Hemoccult Sensa) and an immunochemical test (HemeSelect/FlexSure OBT) offers increased sensitivity with preserved specificity. We propose to evaluate the benefit of adding the combination FOBT to a screening sigmoidoscopy protocol in an estimated 16,000 patients of average risk for colorectal cancer. Patients will be tested with the combination FOBT prior to sigmoidoscopy. Those testing positive will have colonoscopy; negatives will have sigmoidoscopy. Patients not colonoscoped in year 1 will be retested in year 2. Patients will be enrolled over a two year period, receiving up to two combination FOBT, 12 months apart. This is an outcomes oriented study, using computerized Kaiser Permanente databases to track sigmoidoscopy, colonoscopy, and pathology results, and a regional cancer registry to track cancer incidence during a 2 year follow-up period. We will evaluate the following effects of adding the combination FOBT to sigmoidoscopy: (1) the added diagnostic yield; (2) the diagnostic burden (i.e., the colonoscopy rate); and (3) the effect on compliance with screening. Results will be compared with subjects at the same facilities prior to starting the combined strategy (historical controls), to non-random, concurrent controls being screened elsewhere with sigmoidoscopy-only, and to internal controls by using the yield of advanced proximal neoplasms detectable only with the combined strategy. Finally, this study will be used to modify a cost-effectiveness model of CRC screening strategies.